Elevated CCL19/CCR7 Expression During the Disease Process of Primary Sjögren's Syndrome

Liu, Zhenwei; Li, Fengxia; Pan, Axiao; Xue, Huangqi; Jiang, Shan; Zhu, Ce; Jin, Mengmeng; Fang, Jinxia; Zhu, Xiongzhao; Brown, Matthew A.; Wang, Xiaobing

doi:10.3389/fimmu.2019.00795

Cited by 21 publications

(16 citation statements)

References 63 publications

(69 reference statements)

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“…To confirm the robustness of our sequencing results, we next compared the global transcriptomes of the control and pSS glands by utilizing RNA-sequencing (RNA-seq) datasets described here, to additional RNA-seq (Liu et al.) ( 49 ) and microarray array datasets (Min et al.) ( 50 ) that have been previously reported ( Figure 2 and Supplementary Figure S1 ).…”

Section: Resultsmentioning

confidence: 66%

“…We reasoned that this approach would address possible variations between the three datasets due to technical and experimental differences. Indeed, our analysis identified a number of genes common to all three datasets that have been previously demonstrated to play important roles in pSS pathogenesis including several members of the CXC chemokine family of cytokines including CXCL9, CXCL10, CXCL11, CXCL13 ( 15 , 51 , 52 ), members of the guanylate-binding protein family; GBP1 , GBP5 ( 49 , 53 , 54 ), as well as AIM2 ( 55 ), CD52 ( 56 ), and GZMK ( 57 ). To further confirm these results, we performed quantitative reverse-transcription polymerase chain reaction (qRT-PCR) using a subset of patient samples which were included in our RNA-seq analysis to examine the mRNA expression levels of a select number of candidate genes, several of which have been implicated in pSS pathogenesis.…”

Section: Resultsmentioning

confidence: 99%

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Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren’s Syndrome

et al. 2021

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Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized primarily by immune-mediated destruction of exocrine tissues, such as those of the salivary and lacrimal glands, resulting in the loss of saliva and tear production, respectively. This disease predominantly affects middle-aged women, often in an insidious manner with the accumulation of subtle changes in glandular function occurring over many years. Patients commonly suffer from pSS symptoms for years before receiving a diagnosis. Currently, there is no effective cure for pSS and treatment options and targeted therapy approaches are limited due to a lack of our overall understanding of the disease etiology and its underlying pathology. To better elucidate the underlying molecular nature of this disease, we have performed RNA-sequencing to generate a comprehensive global gene expression profile of minor salivary glands from an ethnically diverse cohort of patients with pSS. Gene expression analysis has identified a number of pathways and networks that are relevant in pSS pathogenesis. Moreover, our detailed integrative analysis has revealed a primary Sjögren’s syndrome molecular signature that may represent important players acting as potential drivers of this disease. Finally, we have established that the global transcriptomic changes in pSS are likely to be attributed not only to various immune cell types within the salivary gland but also epithelial cells which are likely playing a contributing role. Overall, our comprehensive studies provide a database-enriched framework and resource for the identification and examination of key pathways, mediators, and new biomarkers important in the pathogenesis of this disease with the long-term goals of facilitating earlier diagnosis of pSS and to mitigate or abrogate the progression of this debilitating disease.

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Section: Resultsmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren’s Syndrome

et al. 2021

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“…Moreover, the KEGG pathway enrichment analysis of common DEGs also suggested their relevance in the pathogenesis of pSS. Chemokine signaling pathway was essential for maintaining the function and interaction of T lymphocytes (Ward and Westwick, 1998), and cytokine CCL19 was identified as a biomarker of immunological activation in pSS with its chemokine receptor CCR7 in our other study (Liu et al, 2019). It has been reported that adhesion molecules, such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, were indispensable factors for lymphocyte recruitment, glandular damage, and the development of vasculitis in pSS, indicating the importance of CAM pathway in the mechanism of pSS (Turkcapar et al, 2005).…”

Section: Discussionmentioning

confidence: 69%

“…Similarly, the branchpoint-site single-nucleotide polymorphisms rs17266594 and rs10516487 in the B cell scaffold protein with ankyrin repeats 1 (BANK1) gene have been testified to be associated with various autoimmune diseases including SLE (Guan et al, 2011), RA (Orozco et al, 2009), and SSc (Rueda et al, 2010). Moreover, in our other study, we had found that elevated CCL19/CCR7 expression in the salivary gland associated with anti-SSA/Ro antibody and IgG levels in pSS patients could serve as markers of immunological activation in pSS (Liu et al, 2019). Interestingly, although the inducible costimulatory molecule (ICOS), as a member of the CD28 family of coreceptor molecules, has been suggested to induce the difference of interleukin 17 (IL-17)-producing helper T cells (Th17 cells) and follicular helper T cells (Tfh cells), there are rare studies reporting the relativity between ICOS and pSS (Dong et al, 2001;Bauquet et al, 2009).…”

Section: Discussionmentioning

confidence: 83%

Transcriptome Sequencing Reveals Potential Roles of ICOS in Primary Sjögren’s Syndrome

Luo

Liao

Zhang

et al. 2020

Front. Cell Dev. Biol.

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Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by exocrine gland damage and extraglandular involvements. To identify potential biomarkers for the early detection of pSS and to further investigate the potential roles of the biomarkers in the progression of pSS, our previous RNA sequencing data and four microarray data of salivary glands (SGs) were combined for integrative transcriptome analysis between pSS and non-pSS. Differential gene expression analysis, gene co-expression network analysis, and pathway analysis were conducted to detect hub genes, which were subsequently investigated in peripheral blood mononuclear cell (PBMC) and plasma. Correlation analysis, single-gene Gene Set Enrichment Analysis, and receiver operating characteristic (ROC) curve were applied to investigate the potential function of the hub genes and their classification capacity for pSS. A total of 51 common up-regulated genes were identified among different pSS cohorts. A key module was found to be the most closely linked to pSS, which was significantly associated with inflammation-related pathways. Seven overlapped hub genes (ICOS, SELL, CR2, BANK1, MS4A1, ZC3H12D, and CCR7) were identified, among which ICOS was demonstrated to be involved in most crucial immune pathways. ICOS was up-regulated not only in SGs but also in PBMC and plasma in pSS, and the expression of ICOS was closely associated with lymphocytic infiltration in SGs and disease activity of pSS patients. It showed a strong classification capacity with classic clinical index in SGs (ROC curve 0.9821) and significant distinct discrimination in PBMC (ROC curve 0.9107). These findings are expected to gain a further insight into the pathogenesis of pSS and provide a promising candidate for the early detection of pSS.

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“…RNA-seq raw reads were processed in a similar manner as previously described. 53,54 Both 3 0 and 5 0 adapter contaminants were removed by Cutadapt, and the full-length reads were processed as FASTA format using an in-house pipeline. 55 After preprocessing, the quality of these reads was evaluated by FastQC and further visualized by SplicingViewer software.…”

Section: Data Preprocessingmentioning

confidence: 99%

Time‐resolved mRNA and miRNA expression profiling reveals crucial coregulation of molecular pathways involved in epithelial–pneumococcal interactions

Lin

Lei

et al. 2020

Immunol Cell Biol

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Streptococcus pneumoniae is a major causative agent of pneumonia worldwide and its complex interaction with the lung epithelium has not been thoroughly characterized. In this study, we exploited both RNA-sequencing and microRNA (miRNA)-sequencing approaches to monitor the transcriptional changes in human lung alveolar epithelial cells infected by S. pneumoniae in a timeresolved manner. A total of 1330 differentially expressed (DE) genes and 45 DE miRNAs were identified in all comparisons during the infection process. Clustering analysis showed that all DE genes were grouped into six clusters, several of which were primarily involved in inflammatory or immune responses. In addition, target gene enrichment analyses identified 11 transcription factors that were predicted to link at least one of four clusters, revealing transcriptional coregulation of multiple processes or pathways by common transcription factors. Notably, pharmacological treatment suggested that phosphorylation of p65 is important for optimal transcriptional regulation of target genes in epithelial cells exposed to pathogens. Furthermore, networkbased clustering analysis separated the DE genes negatively regulated by DE miRNAs into two functional modules (M1 and M2), with an enrichment in immune responses and apoptotic signaling pathways for M1. Integrated network analyses of potential regulatory interactions in M1 revealed that multiple DE genes related to immunity and apoptosis were regulated by multiple miRNAs, indicating the coordinated regulation of multiple genes by multiple miRNAs. In conclusion, time-series expression profiling of messenger RNA and miRNA provides a wealth of information for global transcriptional changes, and offers comprehensive insight into the molecular mechanisms underlying host-pathogen interactions.

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Elevated CCL19/CCR7 Expression During the Disease Process of Primary Sjögren's Syndrome

Cited by 21 publications

References 63 publications

Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren’s Syndrome

Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren’s Syndrome

Transcriptome Sequencing Reveals Potential Roles of ICOS in Primary Sjögren’s Syndrome

Time‐resolved mRNA and miRNA expression profiling reveals crucial coregulation of molecular pathways involved in epithelial–pneumococcal interactions

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